Presentation is loading. Please wait.

Presentation is loading. Please wait.

Synthetic mimetics of protein secondary structure domains by Nathan T. Ross, William P. Katt, and Andrew D. Hamilton Philosophical Transactions A Volume.

Similar presentations


Presentation on theme: "Synthetic mimetics of protein secondary structure domains by Nathan T. Ross, William P. Katt, and Andrew D. Hamilton Philosophical Transactions A Volume."— Presentation transcript:

1 Synthetic mimetics of protein secondary structure domains by Nathan T. Ross, William P. Katt, and Andrew D. Hamilton Philosophical Transactions A Volume 368(1914):989-1008 March 13, 2010 ©2010 by The Royal Society

2 N-substituted glycine monomers used for the construction of helical peptoids by the Barron laboratory. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

3 Cysteine and histidine mimetic peptoids bind to a zinc atom, bringing two helices into a bundle. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

4 Structural insights into the assembly of β-peptides can be gained from X-ray crystal structures depicting the three-dimensional structure of fully assembled β-peptides such as this one from Goodman et al. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

5 Walensky stapled peptide, which had increased affinity for Bcl-2 over comparable unstapled compounds. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

6 NMR solution structure of a stapled peptide (orange) bound to capsid (blue). Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

7 Peptide sequences used by Shepherd et al. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

8 Recent α-helix mimetics from the Hamilton (1–3), Rebek (4–9) and Konig (10) groups. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

9 (a) Overlay of the X-ray crystal structure of a trismethyl 5-6-5 imidazole-phenyl-thiazole derivative with key contact residues from Dbs. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

10 A superhelix antenna array. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

11 Structure of the trishomocubane amino acid used by Albericio et al. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

12 (a) Generic spyrocycle scaffold for β-turn mimicry. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

13 (a) An azobenzene turn inducer as a trans-isomer. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

14 The use of a ferrocine tethered between two cyclopentadienyl terminated amino acid chains that feature a Gly-X-X motif allowing for β-sheet formation with cross-strand hydrogen bonds. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

15 Metal tethered phosphine-based turn mimetic developed by Laungani et al. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

16 X-ray crystal structure of Smac (blue/black) bound to XIAP-BIR domain (orange/magenta), AVPI residues of Smac are shown in green (pdb 1G73; Wu et al. 2000). Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

17 Structures of Zobel et al. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

18 Initial lead compounds from the Deshayes group: (a) AVPW and (b) the final inhibitor 13, both bound to a BIR domain as found in XIAP. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society

19 Smac mimetics from the Wang group, where dimerization of Smac mimetics has been shown to be an effective means of increasing compound potency and efficacy. Nathan T. Ross et al. Phil. Trans. R. Soc. A 2010;368:989- 1008 ©2010 by The Royal Society


Download ppt "Synthetic mimetics of protein secondary structure domains by Nathan T. Ross, William P. Katt, and Andrew D. Hamilton Philosophical Transactions A Volume."

Similar presentations


Ads by Google